MCID: APP015
MIFTS: 52

Apparent Mineralocorticoid Excess

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Nephrological diseases, Endocrine diseases, Metabolic diseases

Aliases & Classifications for Apparent Mineralocorticoid Excess

MalaCards integrated aliases for Apparent Mineralocorticoid Excess:

Name: Apparent Mineralocorticoid Excess 54 12 50 56 71 29 13 42 69
Cortisol 11-Beta-Ketoreductase Deficiency 12 50 24 71 69
Apparent Mineralocorticoid Excess Syndrome 12 24 14
Ame 50 24 71
11-Beta-Hydroxysteroid Dehydrogenase Deficiency Type 2 12 56
Mineralocorticoid Excess Syndrome, Apparent 42 69
Ulick Syndrome 12 56
Ame1 24 71
Syndrome of Apparent Mineralocorticoid Excess 12
Ame 1 50
Ape 12

Characteristics:

Orphanet epidemiological data:

56
apparent mineralocorticoid excess
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset usually in infancy or childhood
favorable response to spironolactone


HPO:

32
apparent mineralocorticoid excess:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 218030
Disease Ontology 12 DOID:0090121 DOID:4367
ICD10 33 E26.1
NCIt 47 C123231
SNOMED-CT 64 237770005
Orphanet 56 ORPHA320
MESH via Orphanet 43 C537422 D043204
UMLS via Orphanet 70 C0342488 C2936861 C3887949
ICD10 via Orphanet 34 E26.1
MedGen 40 C2936861

Summaries for Apparent Mineralocorticoid Excess

OMIM : 54
Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone (review by Ferrari, 2010). (218030)

MalaCards based summary : Apparent Mineralocorticoid Excess, also known as cortisol 11-beta-ketoreductase deficiency, is related to antiphospholipid syndrome and catastrophic antiphospholipid syndrome, and has symptoms including short stature, failure to thrive and hypokalemia. An important gene associated with Apparent Mineralocorticoid Excess is HSD11B2 (Hydroxysteroid 11-Beta Dehydrogenase 2), and among its related pathways/superpathways are Metabolism of steroid hormones and Aldosterone-regulated sodium reabsorption. The drugs Licorice and Enoxolone have been mentioned in the context of this disorder. Affiliated tissues include kidney and adrenal gland, and related phenotypes are Decreased shRNA abundance and behavior/neurological

Disease Ontology : 12 An adrenal gland hyperfunction characterized by decreased conversion of biologically active cortisol to inactive cortisone resulting in low aldosterone levels, metabolic alkalosis, hypernatremia, hypokalemia and early-onset severe hypertension that has material basis in homozygous or compound heterozygous mutation in the HSD11B2 gene on chromosome 16.

UniProtKB/Swiss-Prot : 71 Apparent mineralocorticoid excess: An autosomal recessive form of low-renin hypertension. It is usually diagnosed within the first years of life and is characterized by polyuria and polydipsia, failure to thrive, hypernatremia, severe hypertension with low renin and aldosterone levels, profound hypokalemia with metabolic alkalosis, and most often nephrocalcinosis.

Wikipedia : 72 Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder causing hypertension (high... more...

Related Diseases for Apparent Mineralocorticoid Excess

Diseases related to Apparent Mineralocorticoid Excess via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 92)
id Related Disease Score Top Affiliating Genes
1 antiphospholipid syndrome 11.9
2 catastrophic antiphospholipid syndrome 11.5
3 ablepharon-macrostomia syndrome 11.5
4 autoimmune polyendocrine syndrome, type ii 11.4
5 autoimmune polyendocrine syndrome type 1 11.2
6 acute mountain sickness 11.1
7 autoimmune polyendocrine syndrome 11.1
8 amenorrhea 11.1
9 glycosylphosphatidylinositol deficiency 11.0
10 fryns microphthalmia syndrome 10.9
11 dysplastic nevus syndrome 10.8
12 hemosiderosis 10.8
13 periapical periodontitis 10.7
14 autoimmune polyglandular syndrome type 3 10.7
15 microlissencephaly iii 10.7
16 autoimmune polyendocrinopathy type 4 10.7
17 autoimmune polyendocrinopathy type 3 10.7
18 autoimmune polyendocrinopathy syndrome , type i, with or without reversible metaphyseal dysplasia 10.7
19 marden-walker syndrome 10.6 NR3C2 REN
20 hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy 10.6 NR3C2 REN
21 long qt syndrome 13 10.6 NR3C2 REN
22 myopia 25, autosomal dominant 10.5 NR3C1 NR3C2
23 bronchiectasis with or without elevated sweat chloride 2 10.5 NR3C2 REN
24 urinary bladder posterior wall cancer 10.3 PIK3C2A REN
25 acute liver failure 10.3 PIK3C2A REN
26 bestrophinopathy 10.2 CLCNKB REN
27 leukemia 10.2
28 myopathy of extraocular muscle 10.2 HSD11B1 NR3C1 NR3C2
29 microphthalmia, isolated, with coloboma 7 10.2 NR3C2 PIK3C2A REN
30 craniosynostosis 10.1 NR3C2 PIK3C2A REN
31 spondyloepimetaphyseal dysplasia, faden-alkuraya type 10.1 CLCNKB REN
32 monosomy 13q34 10.1 POMC REN
33 hypodontia of incisors and premolars 10.1 POMC REN
34 carotid artery thrombosis 10.1 POMC REN
35 retinal vein occlusion 10.1 ATP6V0A4 NR3C2 REN
36 cholangiolocellular carcinoma 10.1 POMC REN
37 pyelonephritis 10.1 PIK3C2A REN
38 traumatic glaucoma 10.1 HSD11B2 POMC
39 dressler's syndrome 10.0 POMC REN
40 familial hypopituitarism 10.0 POMC REN
41 uterine corpus adenocarcinofibroma 10.0 POMC REN
42 actinobacillosis 10.0 NR3C1 POMC
43 liddle syndrome 10.0
44 hypothyroidism 10.0
45 pancreatitis 10.0
46 angioid streaks of choroid 9.9 PIK3C2A POMC
47 acute myocarditis 9.9 HSD11B1 POMC
48 bronchiectasis with or without elevated sweat chloride 1 9.9 HSD11B2 NR3C1 NR3C2 REN
49 cold-induced sweating syndrome 2 9.9 NR3C1 POMC
50 acute myeloid leukemia, susceptibility, gata2-related 9.9 HSD11B1 POMC

Graphical network of the top 20 diseases related to Apparent Mineralocorticoid Excess:



Diseases related to Apparent Mineralocorticoid Excess

Symptoms & Phenotypes for Apparent Mineralocorticoid Excess

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Laboratory- Abnormalities:
hypokalemia
low plasma renin activity
decreased serum aldosterone
increased urinary cortisol/cortisone ratio

Cardiovascular- Vascular:
hypertension

Genitourinary- Kidneys:
increased renal salt reabsorption
kidney failure if untreated

Growth- Other:
failure to thrive

Growth- Weight:
low birth weight

Metabolic Features:
metabolic alkalosis


Clinical features from OMIM:

218030

Human phenotypes related to Apparent Mineralocorticoid Excess:

32 (show all 9)
id Description HPO Frequency HPO Source Accession
1 short stature 32 HP:0004322
2 failure to thrive 32 HP:0001508
3 hypokalemia 32 HP:0002900
4 hypertension 32 HP:0000822
5 small for gestational age 32 HP:0001518
6 metabolic alkalosis 32 HP:0200114
7 decreased circulating aldosterone level 32 HP:0004319
8 decreased circulating renin level 32 HP:0003351
9 hypertensive retinopathy 32 HP:0001095

GenomeRNAi Phenotypes related to Apparent Mineralocorticoid Excess according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance GR00297-A 8.92 CLCNKB HSD11B2 HSD17B6 PIK3C2A

MGI Mouse Phenotypes related to Apparent Mineralocorticoid Excess:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.92 ATP6V0A4 HSD11B1 HSD11B2 NR3C1 NR3C2 PIK3C2A
2 homeostasis/metabolism MP:0005376 9.81 NR3C2 PIK3C2A POMC REN ATP6V0A4 CLCNKB
3 cardiovascular system MP:0005385 9.8 HSD11B1 HSD11B2 NR3C1 NR3C2 PIK3C2A POMC
4 muscle MP:0005369 9.35 HSD11B1 HSD11B2 NR3C1 NR3C2 REN
5 renal/urinary system MP:0005367 9.23 ATP6V0A4 CLCNKB HSD11B2 NR3C1 NR3C2 PIK3C2A

Drugs & Therapeutics for Apparent Mineralocorticoid Excess

Drugs for Apparent Mineralocorticoid Excess (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Licorice Approved, Nutraceutical Phase 2, Phase 3
2
Enoxolone Investigational Phase 2, Phase 3 471-53-4 18526330
3 Anti-Inflammatory Agents Phase 2, Phase 3
4 Hormone Antagonists Phase 2, Phase 3
5 Hormones Phase 2, Phase 3
6 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
7 Mineralocorticoids Phase 2, Phase 3
8
Cortisone acetate Approved 1950-04-4, 50-04-4 5745
9
Hydrocortisone Approved, Vet_approved 50-23-7 5754 657311
10
Butyric Acid Experimental 107-92-6 264
11 Cortisol succinate
12
Cortisone 53-06-5 222786
13 Hydrocortisone 17-butyrate 21-propionate
14 Hydrocortisone acetate
15 Hydrocortisone-17-butyrate

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 The Role of Mineralocorticoid Receptors in Vascular Function Completed NCT00759525 Phase 2, Phase 3 Glycyrrhetic Acid;Placebo
2 Natural History of Apparent Mineralocorticoid Excess Syndrome Completed NCT00474942
3 An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio Recruiting NCT02939144

Search NIH Clinical Center for Apparent Mineralocorticoid Excess

Cochrane evidence based reviews: mineralocorticoid excess syndrome, apparent

Genetic Tests for Apparent Mineralocorticoid Excess

Genetic tests related to Apparent Mineralocorticoid Excess:

id Genetic test Affiliating Genes
1 Apparent Mineralocorticoid Excess 29
2 Apparent Mineralocorticoid Excess Syndrome 24 HSD11B2

Anatomical Context for Apparent Mineralocorticoid Excess

MalaCards organs/tissues related to Apparent Mineralocorticoid Excess:

39
Kidney, Adrenal Gland

Publications for Apparent Mineralocorticoid Excess

Articles related to Apparent Mineralocorticoid Excess:

(show top 50) (show all 61)
id Title Authors Year
1
Liquorice-induced apparent mineralocorticoid excess presenting in the emergency department. ( 28148579 )
2017
2
Apparent mineralocorticoid excess caused by a novel mutation in 11I^-hydroxysteroid dehydrogenase type 2 gene. ( 28121843 )
2017
3
Apparent mineralocorticoid excess and the long term treatment of genetic hypertension. ( 26892095 )
2016
4
Apparent Mineralocorticoid Excess Syndrome: A Case of Resistant Hypertension From Licorice Tea Consumption. ( 27251761 )
2016
5
A novel mutation in HSD11B2 causes apparent mineralocorticoid excess in an Omani kindred. ( 27526338 )
2016
6
Apparent mineralocorticoid excess. ( 26956190 )
2016
7
Apparent Mineralocorticoid Excess by a Novel Mutation and Epigenetic Modulation by HSD11B2 Promoter Methylation. ( 26126204 )
2015
8
Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess. ( 25593612 )
2015
9
A case of iatrogenic Cushing syndrome and apparent mineralocorticoid excess presenting with accelerated hypertension and proteinuria. ( 25201428 )
2014
10
Remission of hypertension and electrolyte abnormalities following renal transplantation in a patient with apparent mineralocorticoid excess well documented throughout childhood. ( 23945123 )
2014
11
Apparent Mineralocorticoid Excess Caused by a Novel Mutation in 11-I^ Hydroxysteroid Dehydrogenase Type 2 Enzyme: Its Genetics and Response to Therapy. ( 24936560 )
2014
12
Apparent mineralocorticoid excess (AME) syndrome. ( 23665601 )
2013
13
Apparent mineralocorticoid excess syndrome: report of one family with three affected children. ( 23329753 )
2012
14
Apparent mineralocorticoid excess: time of manifestation and complications despite treatment. ( 21536617 )
2011
15
Apparent mineralocorticoid excess - update. ( 21691952 )
2011
16
Familial glucocorticoid receptor haploinsufficiency by non-sense mediated mRNA decay, adrenal hyperplasia and apparent mineralocorticoid excess. ( 21042587 )
2010
17
A switch in the mechanism of hypertension in the syndrome of apparent mineralocorticoid excess. ( 18032795 )
2008
18
Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene. ( 19169481 )
2008
19
Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess. ( 17314322 )
2007
20
Apparent mineralocorticoid excess manifested in an elderly patient with hypothyroidism. ( 17198920 )
2007
21
[From gene to disease; 'apparent mineralocorticoid excess' syndrome, a syndrome with an apparent excess of mineral corticoids]. ( 17447595 )
2007
22
Apparent mineralocorticoid excess manifested in an elderly patient with hypothyroidism. ( 17516565 )
2007
23
Apparent mineralocorticoid excess: report of six new cases and extensive personal experience. ( 17035606 )
2006
24
Apparent mineralocorticoid excess syndrome: an overview. ( 15761540 )
2004
25
In vitro expression studies of a novel mutation delta299 in a patient affected with apparent mineralocorticoid excess. ( 15126515 )
2004
26
Distinction between Liddle syndrome and apparent mineralocorticoid excess. ( 14625721 )
2004
27
Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population. ( 15134813 )
2004
28
Late-onset apparent mineralocorticoid excess caused by novel compound heterozygous mutations in the HSD11B2 gene. ( 12860834 )
2003
29
Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. ( 12788846 )
2003
30
The distinction between Liddle syndrome and apparent mineralocorticoid excess. ( 12759812 )
2003
31
Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and cortisone. ( 11227727 )
2001
32
Apparent mineralocorticoid excess. ( 11306334 )
2001
33
Does kidney transplantation normalise cortisol metabolism in apparent mineralocorticoid excess syndrome? ( 11005270 )
2000
34
Liquorice-induced sodium retention. Merely an acquired condition of apparent mineralocorticoid excess? A case report. ( 11202632 )
2000
35
Hormonal hypertension in children: 11beta-hydroxylase deficiency and apparent mineralocorticoid excess. ( 11154148 )
2000
36
Nephrocalcinosis and renal cysts associated with apparent mineralocorticoid excess syndrome. ( 11095013 )
2000
37
[Syndrome of apparent mineralocorticoid excess caused by a deficiency of 11 beta-hydroxysteroid dehydrogenase: clinical and genetic study in a Chilean family followed for 19 years]. ( 10883518 )
2000
38
Steroid disorders in children: congenital adrenal hyperplasia and apparent mineralocorticoid excess. ( 10536001 )
1999
39
Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess. ( 10523339 )
1999
40
Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess. ( 10489390 )
1999
41
Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. ( 9661590 )
1998
42
Molecular basis for hypertension in the 'type II variant' of apparent mineralocorticoid excess. ( 9683587 )
1998
43
The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess. ( 9851783 )
1998
44
[A case of apparent mineralocorticoid excess caused by type 2 11 beta- hydroxysteroid dehydrogenase deficiency]. ( 9404418 )
1997
45
Apparent mineralocorticoid excess in a Brazilian kindred: hypertension in the heterozygote state. ( 9431844 )
1997
46
A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. ( 9398712 )
1997
47
11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. ( 9034789 )
1997
48
Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene. ( 8538347 )
1996
49
Apparent mineralocorticoid excess due to 11 beta-hydroxysteroid dehydrogenase deficiency: a possible cause of intrauterine growth retardation. ( 8729536 )
1996
50
Apparent mineralocorticoid excess: genotype is correlated with biochemical phenotype. ( 8641723 )
1996

Variations for Apparent Mineralocorticoid Excess

UniProtKB/Swiss-Prot genetic disease variations for Apparent Mineralocorticoid Excess:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 HSD11B2 p.Arg208Cys VAR_006958 rs121917780
2 HSD11B2 p.Arg213Cys VAR_006959 rs28934591
3 HSD11B2 p.Leu179Arg VAR_015635
4 HSD11B2 p.Ser180Phe VAR_015636
5 HSD11B2 p.Arg186Cys VAR_015637 rs768507002
6 HSD11B2 p.Arg208His VAR_015638 rs28934592
7 HSD11B2 p.Ala237Val VAR_015640
8 HSD11B2 p.Asp244Asn VAR_015641
9 HSD11B2 p.Leu250Arg VAR_015642
10 HSD11B2 p.Arg279Cys VAR_015644 rs28934594
11 HSD11B2 p.Ala328Val VAR_015645
12 HSD11B2 p.Tyr338His VAR_015646 rs387907117
13 HSD11B2 p.Asp223Asn VAR_066514 rs121917833
14 HSD11B2 p.Arg337Cys VAR_066515 rs121917781

ClinVar genetic disease variations for Apparent Mineralocorticoid Excess:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 HSD11B2 NM_000196.3(HSD11B2): c.622C> T (p.Arg208Cys) single nucleotide variant Pathogenic rs121917780 GRCh37 Chromosome 16, 67470003: 67470003
2 HSD11B2 NM_000196.3(HSD11B2): c.637C> T (p.Arg213Cys) single nucleotide variant Pathogenic rs28934591 GRCh37 Chromosome 16, 67470018: 67470018
3 HSD11B2 NM_000196.3(HSD11B2): c.1009C> T (p.Arg337Cys) single nucleotide variant Pathogenic rs121917781 GRCh37 Chromosome 16, 67470697: 67470697
4 HSD11B2 NM_000196.3(HSD11B2): c.623G> A (p.Arg208His) single nucleotide variant Pathogenic rs28934592 GRCh37 Chromosome 16, 67470004: 67470004
5 HSD11B2 NM_000196.3(HSD11B2): c.1010_1012delGCT (p.Arg337_Tyr338delinsHis) deletion Pathogenic rs397509434 GRCh37 Chromosome 16, 67470698: 67470700
6 HSD11B2 NM_000196.3(HSD11B2): c.835C> T (p.Arg279Cys) single nucleotide variant Pathogenic rs28934594 GRCh37 Chromosome 16, 67470523: 67470523
7 HSD11B2 NM_000196.3(HSD11B2): c.667G> A (p.Asp223Asn) single nucleotide variant Pathogenic rs121917833 GRCh37 Chromosome 16, 67470154: 67470154
8 HSD11B2 NM_000196.3(HSD11B2): c.895_897delTAC (p.Tyr299del) deletion Pathogenic rs794726670 GRCh37 Chromosome 16, 67470583: 67470585
9 HSD11B2 NM_000196.3(HSD11B2): c.664+14C> T single nucleotide variant Pathogenic rs376023420 GRCh37 Chromosome 16, 67470059: 67470059
10 HSD11B2 NM_000196.3(HSD11B2): c.1012T> C (p.Tyr338His) single nucleotide variant Pathogenic rs387907117 GRCh37 Chromosome 16, 67470700: 67470700
11 HSD11B2 NM_000196.3(HSD11B2): c.77_78delCA (p.Ser26Terfs) deletion Pathogenic rs794726684 GRCh37 Chromosome 16, 67465228: 67465229

Expression for Apparent Mineralocorticoid Excess

Search GEO for disease gene expression data for Apparent Mineralocorticoid Excess.

Pathways for Apparent Mineralocorticoid Excess

GO Terms for Apparent Mineralocorticoid Excess

Biological processes related to Apparent Mineralocorticoid Excess according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 excretion GO:0007588 8.96 ATP6V0A4 CLCNKB
2 glucocorticoid biosynthetic process GO:0006704 8.62 HSD11B1 HSD11B2

Molecular functions related to Apparent Mineralocorticoid Excess according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 steroid hormone receptor activity GO:0003707 9.16 NR3C1 NR3C2
2 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity GO:0003845 8.96 HSD11B1 HSD11B2
3 steroid binding GO:0005496 8.8 HSD11B2 NR3C1 NR3C2

Sources for Apparent Mineralocorticoid Excess

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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